In a recent study entitled “FGL2 as a Multimodality Regulator of Tumor-Mediated Immune Suppression and Therapeutic Target in Gliomas,” researchers at The University of Texas MD Anderson Cancer Center showed that FGL2 protein is a crucial immune-suppressive factor in glioblastoma multiforme (GBM) cancer. As such, blocking FGL2 may promote GBM patients’ enhanced survival. The study was published in the Journal of the National Cancer Institute.
In this study, a research team at The University of Texas MD Anderson Cancer Center showed that FGL2 (short for Fibrinogen-like protein 2), commonly expressed in cancers, acts as an immune-suppressor in glioblastoma multiforme (GBM), allowing the tumor to grow by suppressing tumor-targeted immune responses. FGL2 acts by enhancing the expression of genes encoding for immune checkpoints, i.e., a collection of factors that are key for maintaining body self-tolerance by controlling the duration and amplitude of the immune responses.
The team used mouse models but also human tumor samples and The Cancer Genome Atlas (TCGA) glioma database, a comprehensively project launched in 2006 with the objective to characterize the genomic and molecular characteristics of both ovarian cancer and glioblastoma multiforme.
The authors found that patients with high levels of FGL2 expression in glioma tissues exhibited lower overall survival. To evaluate the functional relevance of blocking FGL2 expression, authors treated mouse models for glioblastoma with an anti-FGL2 antibody. They observed mice median survival increased; specifically mice lived 27 days more when compared to 17 days of the control antibody.
The team highlights that because FGL2 functions as a key immune-suppressive modulator developing future immunotherapeutics against FGL2 may promote patients’ survival.
Shulin Li, Ph.D., professor of Pediatrics and study lead author commented, “It is well known that cancer evades immune surveillance by exploiting a series of editing mechanisms to avoid immune detection and eradication. One such mechanism is to hijack an immune cell’s checkpoints, subverting the immune system and allowing tumor growth.”
Amy Heimberger, M.D., professor of Neurosurgery and also an author added, “The average survival time in mice treated with the antibody was significantly longer than those receiving an alternative control antibody. Interestingly, four of 17 mice treated with FGL2 antibody were completely tumor free.”